RTI International proposes to establish an efficient and productive Medication Initiative for Tobacco Dependence Product Development Partnership (MITD-PDP) with the goal of developing safe and effective medications for the treatment of tobacco dependence. RTI will serve as Managing Partner, bringing to the formation of this partnership extensive experience and demonstrated success in the establishment and operation of private-public partnerships, research in tobacco dependence, and the development of medications in the context of a PDP. During the UH2 Phase of the project, RTI will assess the scientific opportunities for drug discovery and development for tobacco dependence and will prepare a comprehensive plan for the MITD-PDP organization model, roles and responsibilities, processes, and opportunities for support. RTI will summarize these results in a comprehensive business plan and informed research and development strategy, both critical for the next phase of the partnership. The UH3 Phase will implement the business plan and research and development strategy of the UH2 phase, focusing on the formation of an efficient, productive organization;creating a strong drug development portfolio;and establishing a broad network and partnerships to accomplish these goals. To reduce both the cost and attrition rate of the PDP's therapeutic development program, we will utilize a model based on identifying therapeutics at different stages of development (preclinical, clinical Phase I/II and Phase III) to build a pipeline with reduced development time, cost and risk. This approach will ensure that the pipeline contains one or more therapeutics at each stage of development and implement a constant flow of compounds progressing to New Drug Application approval. To provide the funding needed to support the costly development of later stage medications, the MITD-PDP will seek to enhance funding and expand the PDP by approaching a diverse range of funding organizations that may include non-NIH government agencies and philanthropic groups. We will also pursue codevelopment partnerships for the MITD-PDP with industry to leverage their resources and expertise. These funding efforts will leverage the NIDA funding with an equivalent level of additional funding to enable an enhanced and self-sustaining MITD-PDP research and development program. The proposed Principal Investigator, Dr. Doris Rouse, brings extensive experience in the establishment and operation of PDPs and the development of medications. PUBLIC HEALTH RELEVANCE: To reduce the estimated 435,000 annual deaths in the United States caused by smoking-related illnesses, improved methods to help individuals stop smoking are needed. To address this important public health need, the Medication Initiative for Tobacco Dependence (MITD) New Product Development Partnership (PDP) will combine public- and private-sector expertise and resources to accelerate the development and approval of safe and effective new medications to treat tobacco dependence. This partnership between government, industry, and nonprofit research organizations will incorporate the most recent research results in an efficient product development strategy to bring new therapies to market to help relieve the devastating impact tobacco use has on public health.